PMID- 32518273
OWN - NLM
STAT- MEDLINE
DCOM- 20210618
LR  - 20210618
IS  - 2158-3188 (Electronic)
IS  - 2158-3188 (Linking)
VI  - 10
IP  - 1
DP  - 2020 Jun 9
TI  - D-Serine as the gatekeeper of NMDA receptor activity: implications for the 
      pharmacologic management of anxiety disorders.
PG  - 184
LID - 10.1038/s41398-020-00870-x [doi]
LID - 184
AB  - Fear, anxiety, and trauma-related disorders, including post-traumatic stress 
      disorder (PTSD), are quite common and debilitating, with an estimated lifetime 
      prevalence of ~28% in Western populations. They are associated with excessive 
      fear reactions, often including an inability to extinguish learned fear, 
      increased avoidance behavior, as well as altered cognition and mood. There is an 
      extensive literature demonstrating the importance of N-methyl-D-aspartate 
      receptor (NMDAR) function in regulating these behaviors. NMDARs require the 
      binding of a co-agonist, D-serine or glycine, at the glycine modulatory site 
      (GMS) to function. D-serine is now garnering attention as the primary NMDAR 
      co-agonist in limbic brain regions implicated in neuropsychiatric disorders. 
      L-serine is synthesized by astrocytes, which is then transported to neurons for 
      conversion to D-serine by serine racemase (SR), a model we term the 'serine 
      shuttle.' The neuronally-released D-serine is what regulates NMDAR activity. Our 
      review discusses how the systems that regulate the synaptic availability of 
      D-serine, a critical gatekeeper of NMDAR-dependent activation, could be targeted 
      to improve the pharmacologic management of anxiety-related disorders where the 
      desired outcomes are the facilitation of fear extinction, as well as mood and 
      cognitive enhancement.
FAU - Wolosker, Herman
AU  - Wolosker H
AD  - Department of Biochemistry, Rappaport Faculty of Medicine, Technion-Israel 
      Institute of Technology, Haifa, 31096, Israel.
FAU - Balu, Darrick T
AU  - Balu DT
AUID- ORCID: 0000-0003-3505-6832
AD  - Department of Psychiatry, Harvard Medical School, Boston, MA, 02115, USA. 
      dbalu@mclean.harvard.edu.
AD  - Translational Psychiatry Laboratory, McLean Hospital, Belmont, MA, 02478, USA. 
      dbalu@mclean.harvard.edu.
LA  - eng
GR  - 337/19/Israel Science Foundation (ISF)/International
GR  - R01NS098740-02/U.S. Department of Health & Human Services | NIH | National 
      Institute of Neurological Disorders and Stroke (NINDS)/International
GR  - R03 AG063201/AG/NIA NIH HHS/United States
GR  - 1R03AG063201-01/U.S. Department of Health & Human Services | NIH | National 
      Institute on Aging (U.S. National Institute on Aging)/International
GR  - R01 NS098740/NS/NINDS NIH HHS/United States
GR  - 2018-05-107/Whitehall Foundation (Whitehall Foundation, Inc.)/International
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20200609
PL  - United States
TA  - Transl Psychiatry
JT  - Translational psychiatry
JID - 101562664
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 452VLY9402 (Serine)
SB  - IM
MH  - Anxiety Disorders/drug therapy
MH  - Extinction, Psychological
MH  - Fear
MH  - Humans
MH  - *Receptors, N-Methyl-D-Aspartate
MH  - *Serine
PMC - PMC7283225
COIS- D.T.B. served as a consultant for LifeSci Capital and received research support 
      from Takeda Pharmaceuticals. H.W. reports no biomedical financial interests or 
      potential conflicts of interest.
EDAT- 2020/06/11 06:00
MHDA- 2021/06/22 06:00
PMCR- 2020/06/09
CRDT- 2020/06/11 06:00
PHST- 2020/01/16 00:00 [received]
PHST- 2020/05/14 00:00 [accepted]
PHST- 2020/05/04 00:00 [revised]
PHST- 2020/06/11 06:00 [entrez]
PHST- 2020/06/11 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/06/09 00:00 [pmc-release]
AID - 10.1038/s41398-020-00870-x [pii]
AID - 870 [pii]
AID - 10.1038/s41398-020-00870-x [doi]
PST - epublish
SO  - Transl Psychiatry. 2020 Jun 9;10(1):184. doi: 10.1038/s41398-020-00870-x.